Proposed is a two-phase study to examine the association between hepatitis C virus (HCV) infection and subsequent development of type 2 diabetes mellitus. Recent evidence from the third National Health and Nutrition Examination Survey and other studies suggest such an association. Given the high prevalence of HCV infection (approximately 90 percent) in injection drug users (IDUs), this study has tremendous health implications for IDUs. Phase I involves a case-cohort study to determine whether there is an independent causal association between HCV infection and type 2 diabetes in a large cohort of community-based men and women. We will enroll 436 incident diabetes cases and 872 age- matched controls from the Atherosclerosis Risk in Communities (ARIC) study and will assess the presence of HCV antibody from frozen serum samples taken prior to the onset of diabetes. In Phase II, we will test a subset (n=210) of anti-HCV positive individuals from a large cohort of IDUs (AIDS Link to Intravenous Experiences) in Baltimore, Maryland for diabetes. Cases of type 2 diabetes will be compared to age-matched controls for differences in HCV viral characteristics such as HCV RNA, liver enzymes and HCV genotype in an attempt to elucidate the mechanism of this proposed association. The results of this study will drive future epidemiological and physiological research into the role of liver disease in the pathogenesis of diabetes as well as potential diabetes prevention programs in populations such as IDUS who bear most of the burden of the hepatitis C virus epidemic.